Vaccine Therapy and Cyclophosphamide in Treating Patients With Stage II-III Breast or Stage II-IV Ovarian, Primary Peritoneal, or Fallopian Tube Cancer
Recurrent Breast Carcinoma
Recurrent Fallopian Tube Carcinoma
Recurrent Ovarian Carcinoma
Recurrent Primary Peritoneal Carcinoma
Stage IIA Breast Cancer
Stage IIA Fallopian Tube Cancer
Stage IIA Ovarian Cancer
Stage IIB Breast Cancer
Stage IIB Fallopian Tube Cancer
Stage IIB Ovarian Cancer
Stage IIC Fallopian Tube Cancer
Stage IIC Ovarian Cancer
Stage IIIA Breast Cancer
Stage IIIA Fallopian Tube Cancer
Stage IIIA Ovarian Cancer
Stage IIIA Primary Peritoneal Cancer
Stage IIIB Breast Cancer
Stage IIIB Fallopian Tube Cancer
Stage IIIB Ovarian Cancer
Stage IIIB Primary Peritoneal Cancer
Stage IIIC Breast Cancer
Stage IIIC Fallopian Tube Cancer
Stage IIIC Ovarian Cancer
Stage IIIC Primary Peritoneal Cancer
Stage IV Fallopian Tube Cancer
Stage IV Ovarian Cancer
Stage IV Primary Peritoneal Cancer
Other: Laboratory Biomarker Analysis
Biological: Multi-epitope Folate Receptor Alpha Peptide Vaccine
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I Trial of the Safety and Immunogenicity of a Multi-epitope Folate Receptor Alpha Peptide Vaccine Used in Combination With Cyclophosphamide in Subjects Previously Treated for Breast or Ovarian Cancer|
- Proportion of patients who experience severe toxicities (grades 3-5 of the National Cancer Institute's Cancer Therapy Evaluation Program [CTEP] Common Terminology Criteria for Adverse Events, version 4.0) [ Time Frame: Up to 12 months ] [ Designated as safety issue: Yes ]Defined as adverse events that are classified as either unrelated, unlikely to be related, possibly, probably, or definitely related to study treatment. The maximum grade for each type of toxicity will be recorded for each patient, and frequency tables will be reviewed by primary disease site to determine toxicity patterns.
- Disease-free survival [ Time Frame: Time from registration to documentation of disease recurrence, second primary, or death without disease recurrence or second primary, assessed up to 12 months ] [ Designated as safety issue: No ]The distribution of disease-free survival will be estimated using the method of Kaplan-Meier for each disease group (breast cancer; ovarian cancer).
- FRa expression [ Time Frame: Up to 12 months ] [ Designated as safety issue: No ]A 90% binomial confidence interval will be constructed for percentage of patients who develop an immune response among those patients who have FRa positive disease. Similarly, a 90% binomial confidence interval will be constructed for percentage of patients who develop an immune response among those patients who have FRa negative disease.
- Overall survival time [ Time Frame: Time from registration to death due to any cause, assessed up to 12 months ] [ Designated as safety issue: No ]The distribution of overall survival times will be estimated using the method of Kaplan-Meier for each disease group (breast cancer; ovarian cancer).
- Percentage change in plasma concentration of cytokines and chemokines [ Time Frame: Baseline to up to 12 months ] [ Designated as safety issue: No ]The percent change in plasma concentrations of cytokines and chemokines from pre-treatment concentrations will be determined. Will be plotted against time with the points belonging to a particular individual connected. Each graph will be visually inspected for trends across time and difference between treatment regimens.
- FR-alpha -specific antibody response by enzyme linked immunosorbent assay [ Time Frame: Up to 12 months ] [ Designated as safety issue: No ]A vaccine-induced FR-alpha-specific antibody responses will be defined as (1) a 2-fold or greater increase in FR-alpha-specific antibody concentration from pretreatment levels at any point during treatment or (2) FR-alpha-specific antibodies above the lower limit of detection at any point during treatment if pre-treatment levels were non-detectable.
- FR-alpha-specific antibody response by enzyme-linked immunospot [ Time Frame: Up to 12 months ] [ Designated as safety issue: No ]A patient is said to have an antigen-specific response at a given post-treatment time point if one of the following sets of conditions is true: 1) the average antigen specific value at pre-treatment > 0, there is a 2 fold increase in average antigen-specific value at post treatment time relative to antigen specific value at pretreatment, and the post-treatment time point of interest (INT) is wholly above the pre-INT; or (2) the average antigen specific value at pre-treatment =< 0, the average antigen-specific value at post treatment time > 0, and the post-INT is wholly above the pre-INT.
- Percent change in antigen-specific cytokine profiles [ Time Frame: Baseline to up to 12 months ] [ Designated as safety issue: No ]Percent change in plasma concentrations of cytokines from pre-treatment levels will be examined to determine skewing of the T cell response to type 1 helper cell or type 2 helper cell after vaccination.
|Study Start Date:||July 2012|
|Estimated Primary Completion Date:||December 2015 (Final data collection date for primary outcome measure)|
Experimental: Treatment (cyclophosphamide and vaccine therapy)
Patients receive cyclophosphamide PO BID on days 1-7 and 15-21 of course 1. Within 3-5 days, patients receive multi-epitope folate receptor alpha peptide vaccine ID on day 1. Vaccine treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Other Names:Other: Laboratory Biomarker Analysis
Correlative studiesBiological: Multi-epitope Folate Receptor Alpha Peptide Vaccine
Other Name: FR Alpha Peptide Vaccine
I. To assess the safety of administering one cycle of cyclophosphamide and six subsequent monthly vaccinations with a peptide-based vaccine targeting folate receptor (FR)-alpha (multi-epitope folate receptor alpha peptide vaccine).
II. To assess the ability of this vaccination protocol to elicit an immune response as measured by activated FR-alpha-specific T lymphocytes or high-affinity antibodies.
I. To determine FR-alpha expression status of primary tumors when available as formalin-fixed, paraffin-embedded material and whether expression correlates with the ability to generate an immune response.
II. To identify human lymphocyte antigen (HLA) class I binding peptides from FR-alpha that are recognized by lymphocytes from patients prior to and after vaccination.
III. To determine whether cyclophosphamide treatment, prior to vaccination, results in regulatory T cell depletion by assessing regulatory T cells before and immediately after cyclophosphamide treatment.
IV. To compare FR-alpha (FRa) expression levels in tumor removed at primary surgery to FRa expression levels in tumor removed for clinical purposes at disease recurrence. (For ovarian cancer patients whose disease recurs.)
Patients receive cyclophosphamide orally (PO) twice daily (BID) on days 1-7 and 15-21 of course 1. Within 3-5 days, patients receive multi-epitope folate receptor alpha peptide vaccine intradermally (ID) on day 1. Vaccine treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 3, 6, and 12 months.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01606241
|United States, Minnesota|
|Rochester, Minnesota, United States, 55905|
|Principal Investigator:||Matthew Block||Mayo Clinic|